A Study to Evaluate the Safety, Tolerability and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA
Sponsor
BioMarin Pharmaceutical (Industry)
Overall Status
Completed
CT.gov ID
NCT00884949
Collaborator
(none)
20
3
1
23
6.7
0.3
Study Details
Study Description
Brief Summary
This multicenter, open-label study is designed to assess safety, dose-response using pharmacokinetic (PK) and pharmacodynamic (PD) measures, and clinical efficacy of BMN 110 in subjects between 5 and 18 years of age, diagnosed with Mucopolysaccharidosis IVA (MPS IVA).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
20 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Multicenter, Open-label, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of BMN 110 in Subjects With Mucopolysaccharidosis IVA (Morquio Syndrome)
Study Start Date
:
Apr 1, 2009
Actual Primary Completion Date
:
Feb 1, 2011
Actual Study Completion Date
:
Mar 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BMN 110 Within-patient Dose-Escalation |
Drug: BMN 110
Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen:
Weeks 1-12: 0.1 mg/kg/week
Weeks 13-24: 1.0 mg/kg/week
Weeks 25-36: 2.0 mg/kg/week
Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week.
|
Outcome Measures
Primary Outcome Measures
- Subject Incidence of Treatment Emergent AEs [Entire Study, through week 84]
The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA. The safety variable incidence of TEAE is summarized.
Secondary Outcome Measures
- Change From Baseline in 6MWT [Baseline to Weeks 12, 24, 36, 48, 72]
Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes.
- Change From Baseline in 3MSCT [Baseline to Weeks 12, 24, 36, 48, 72]
Change from baseline in the 3-minute Stair Climb Test. Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute.
- Percent Change From Baseline in uKS [Baseline to Weeks 12, 24, 36, 72]
Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100%
- Percent Change From Baseline in MVV [Baseline to Weeks 12, 24, 36, 72]
Percent Change from baseline in Maximum Voluntary Ventilation.
- Percent Change From Baseline in FVC [Baseline to Weeks 12, 24, 36, 72]
Percent Change from baseline in Forced Vital Capacity.
Eligibility Criteria
Criteria
Ages Eligible for Study:
5 Years
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Documented history of reduced GALNS activity relative to the normal range of the laboratory performing the assay, or documented result of molecular genetic testing confirming diagnosis of MPS IVA.
-
Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 16 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
-
Between 5 and 18 years of age, inclusive.
-
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
-
Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study.
-
Willing to perform all study procedures as physically possible.
Exclusion Criteria:
-
Previous hematopoietic stem cell transplant (HSCT).
-
Has known hypersensitivity to BMN 110 or its excipients.
-
Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
-
Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
-
Concurrent disease or condition that would interfere with study participation or safety, including, but not limited to, symptomatic cervical spine instability.
-
Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | United Kingdom | |||
| 2 | London | United Kingdom | |||
| 3 | Manchester | United Kingdom |
Sponsors and Collaborators
- BioMarin Pharmaceutical
Investigators
- Study Director: Celeste Decker, MD, BioMarin Pharmceutical Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00884949
Other Study ID Numbers:
- MOR-002
First Posted:
Apr 21, 2009
Last Update Posted:
Jun 30, 2014
Last Verified:
May 1, 2014
Keywords provided by BioMarin Pharmaceutical
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Period Title: Weeks 1-12: 0.1 mg/kg/Week | |
| STARTED | 20 |
| COMPLETED | 18 |
| NOT COMPLETED | 2 |
| Period Title: Weeks 1-12: 0.1 mg/kg/Week | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
| Period Title: Weeks 1-12: 0.1 mg/kg/Week | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
| Period Title: Weeks 1-12: 0.1 mg/kg/Week | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: |
| Overall Participants | 20 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
8.0
(2.89)
|
| Age, Customized (participants) [Number] | |
| >=4 to <8 years |
10
50%
|
| >=8 to <10 years |
6
30%
|
| >=10 to <=18 years |
4
20%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
40%
|
| Male |
12
60%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
20
100%
|
| Unknown or Not Reported |
0
0%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
9
45%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
9
45%
|
| Other |
2
10%
|
| Region of Enrollment (participants) [Number] | |
| United Kingdom |
20
100%
|
Outcome Measures
| Title | Change From Baseline in 6MWT |
|---|---|
| Description | Change from baseline in meters in 6-minute Walk Test. As a measure of endurance, a 6-minute walk test (6MWT) was performed according to the American Thoracic Society Guidelines. Patients were instructed to walk as far as possible in 6 minutes. |
| Time Frame | Baseline to Weeks 12, 24, 36, 48, 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (all subjects who enrolled in the study). Two patients were either physically (score was designated as 0 m) or developmentally (score was set to missing) unable to perform the 6MWT. The analysis was based on observed cases. |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Measure Participants | 20 |
| Week 12 Change from Baseline (n=19) |
-20.7
(85.95)
|
| Week 24 Change from Baseline (n=17) |
16.3
(71.74)
|
| Week 36 Change from Baseline (n=17) |
13.8
(63.25)
|
| Week 48 Change from Baseline (n=17) |
-4.8
(64.70)
|
| Week 72 Change from Baseline (n=17) |
4.0
(87.24)
|
| Title | Change From Baseline in 3MSCT |
|---|---|
| Description | Change from baseline in the 3-minute Stair Climb Test. Patients walked up stairs that have a railing, which could be used for support, for 3 minutes, with the number of stairs climbed recorded. The test result was the number of steps climbed per minute. |
| Time Frame | Baseline to Weeks 12, 24, 36, 48, 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (all subjects who enrolled in the study). One patient was developmentally unable to perform the 3MSCT and the test scores were set to missing. The analysis was based on observed cases. |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Measure Participants | 20 |
| Week 12 Change from Baseline (n=19) |
0.3
(14.07)
|
| Week 24 Change from Baseline (n=17) |
6.1
(8.66)
|
| Week 36 Change from Baseline (n=17) |
7.8
(13.69)
|
| Week 48 Change from Baseline (n=17) |
9.7
(14.42)
|
| Week 72 Change from Baseline (n=17) |
9.7
(13.91)
|
| Title | Percent Change From Baseline in uKS |
|---|---|
| Description | Percent Change from baseline in Normalized Urine KS. The percent change was calculated (Week X value - baseline value)/baseline value *100% |
| Time Frame | Baseline to Weeks 12, 24, 36, 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases. |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Measure Participants | 20 |
| Week 12 Percent Change from Baseline (n=19) |
-23.2
(19.04)
|
| Week 24 Percent Change from Baseline (n=18) |
-27.9
(17.92)
|
| Week 36 Percent Change from Baseline (n=18) |
-40.6
(20.16)
|
| Week 72 Percent Change from Baseline (n=17) |
-32.2
(17.10)
|
| Title | Percent Change From Baseline in MVV |
|---|---|
| Description | Percent Change from baseline in Maximum Voluntary Ventilation. |
| Time Frame | Baseline to Weeks 12, 24, 36, 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases. |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Measure Participants | 20 |
| Week 12 Percent Change from Baseline (n=14) |
9.9
(21.29)
|
| Week 24 Percent Change from Baseline (n=13) |
11.0
(21.48)
|
| Week 36 Percent Change from Baseline (n=14) |
10.5
(17.43)
|
| Week 72 Percent Change from Baseline (n=14) |
18.4
(20.77)
|
| Title | Percent Change From Baseline in FVC |
|---|---|
| Description | Percent Change from baseline in Forced Vital Capacity. |
| Time Frame | Baseline to Weeks 12, 24, 36, 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat population (all subjects who enrolled in the study). The analysis was based on observed cases. |
| Arm/Group Title | BMN 110 |
|---|---|
| Arm/Group Description | Dose-Escalation Period: Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 in 3 consecutive 12-week dosing intervals, using the following regimen: Weeks 1-12: 0.1 mg/kg/week Weeks 13-24: 1.0 mg/kg/week Weeks 25-36: 2.0 mg/kg/week Continuation Period: Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. |
| Measure Participants | 20 |
| Week 12 Percent Change from Baseline (n=18) |
3.4
(10.85)
|
| Week 24 Percent Change from Baseline (n=16) |
0.2
(16.60)
|
| Week 36 Percent Change from Baseline (n=16) |
10.7
(20.82)
|
| Week 72 Percent Change from Baseline (n=16) |
12.5
(14.88)
|
| Title | Subject Incidence of Treatment Emergent AEs |
|---|---|
| Description | The primary objective of the study was to evaluate the safety of weekly infusions of BMN 110 administered in escalating doses to subjects with MPS IVA. The safety variable incidence of TEAE is summarized. |
| Time Frame | Entire Study, through week 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 0.1 mg/kg/Week | 1.0 mg/kg/Week | 2.0 mg/kg/Week | Continuation Period | Entire Study |
|---|---|---|---|---|---|
| Arm/Group Description | Dose-Escalation Period: Weeks 1-12: 0.1 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 0.1 mg/kg/week | Dose-Escalation Period: Weeks 13-24: 1.0 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 1.0 mg/kg/week | Dose-Escalation Period: Weeks 25-36: 2.0 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 2.0 mg/kg/week | Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. | Entire Study period includes both Dose-Escalation Period and Continuation Period. |
| Measure Participants | 20 | 18 | 18 | 18 | 20 |
| Any AEs |
18
90%
|
18
NaN
|
17
NaN
|
17
NaN
|
20
NaN
|
| Any Study Drug-Related AEs |
12
60%
|
10
NaN
|
7
NaN
|
8
NaN
|
14
NaN
|
| Any SAEs |
6
30%
|
2
NaN
|
8
NaN
|
6
NaN
|
14
NaN
|
| Any Study Drug-Related SAEs |
2
10%
|
1
NaN
|
2
NaN
|
1
NaN
|
4
NaN
|
| Any AEs During Infusion |
15
75%
|
13
NaN
|
10
NaN
|
15
NaN
|
17
NaN
|
| Any SAEs During Infusion |
5
25%
|
0
NaN
|
1
NaN
|
1
NaN
|
6
NaN
|
| Any AEs Causing Study Discontinuation |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Any Study Drug-Related AE Causing Study Discont. |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| AEs Causing Permanent Study Drug Discont. |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Drug-Related AE Causing Permanent StudyDrug Discon |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Any SAEs Causing Study Discontinuation |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Any SAEs Causing Permanent Study Drug Discont. |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Study Drug-Related SAE Causing Study Discont. |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| StudyDrug-Related SAE Causing Permanent DrugDiscon |
1
5%
|
0
NaN
|
0
NaN
|
0
NaN
|
1
NaN
|
| Death |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
0
NaN
|
Adverse Events
| Time Frame | Study Period, through 84 weeks | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All Adverse Events | |||||||||
| Arm/Group Title | 0.1 mg/kg/Week | 1.0 mg/kg/Week | 2.0 mg/kg/Week | Continuation Period | Entire Study | |||||
| Arm/Group Description | Dose-Escalation Period: Weeks 1-12: 0.1 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 0.1 mg/kg/week | Dose-Escalation Period: Weeks 13-24: 1.0 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 1.0 mg/kg/week | Dose-Escalation Period: Weeks 25-36: 2.0 mg/kg/week Subjects will receive a weekly 4- to 5-hour intravenous infusion of BMN 110 2.0 mg/kg/week | Subjects who complete the 36-week Dose-Escalation Period will have the option to continue drug treatment for an additional 36 to 48 weeks. Subjects continuing on treatment after the Dose-Escalation period will receive weekly 4- to 5-hour intravenous infusions of BMN 110 at a dose of 1.0 mg/kg/week. | Entire Study period includes both Dose-Escalation Period and Continuation Period. | |||||
All Cause Mortality |
||||||||||
| 0.1 mg/kg/Week | 1.0 mg/kg/Week | 2.0 mg/kg/Week | Continuation Period | Entire Study | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| 0.1 mg/kg/Week | 1.0 mg/kg/Week | 2.0 mg/kg/Week | Continuation Period | Entire Study | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/20 (30%) | 2/18 (11.1%) | 8/18 (44.4%) | 6/18 (33.3%) | 14/20 (70%) | |||||
| General disorders | ||||||||||
| Gait disturbance | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Infusion related reaction | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 3 | 1/20 (5%) | 4 |
| Immune system disorders | ||||||||||
| Type I hypersensitivity | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Infections and infestations | ||||||||||
| Abdominal abscess | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Abscess limb | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Catheter site infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Implant site infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Lower respiratory tract infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Otitis media | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 |
| Pneumonia | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Road traffic accident | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Knee deformity | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/18 (11.1%) | 2 | 5/20 (25%) | 5 |
| Pain in extremity | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Drug eruption | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Rash generalised | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Rash maculo-papular | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Surgical and medical procedures | ||||||||||
| Abscess drainage | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 |
| Catheterisation venous | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 3/18 (16.7%) | 3 | 0/18 (0%) | 0 | 3/20 (15%) | 3 |
| Vascular disorders | ||||||||||
| Poor venous access | 3/20 (15%) | 3 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 4/20 (20%) | 5 |
Other (Not Including Serious) Adverse Events |
||||||||||
| 0.1 mg/kg/Week | 1.0 mg/kg/Week | 2.0 mg/kg/Week | Continuation Period | Entire Study | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/20 (90%) | 18/18 (100%) | 16/18 (88.9%) | 17/18 (94.4%) | 20/20 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Lymphadenopathy | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 |
| Cardiac disorders | ||||||||||
| Mitral valve disease | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 2/20 (10%) | 2 |
| Tachycardia | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Ear and labyrinth disorders | ||||||||||
| Cerumen impaction | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Deafness neurosensory | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Ear canal erythema | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Ear disorder | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Ear pain | 1/20 (5%) | 1 | 1/18 (5.6%) | 2 | 1/18 (5.6%) | 3 | 5/18 (27.8%) | 10 | 5/20 (25%) | 16 |
| External ear disorder | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Hyperacusis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Hypoacusis | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Inner ear disorder | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Motion sickness | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Otorrhoea | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Tinnitus | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Endocrine disorders | ||||||||||
| Autoimmune thyroiditis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Eye disorders | ||||||||||
| Conjunctivitis | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Eye discharge | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Eyelid cyst | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 3/20 (15%) | 3 | 1/18 (5.6%) | 2 | 1/18 (5.6%) | 3 | 1/18 (5.6%) | 2 | 4/20 (20%) | 10 |
| Abdominal pain upper | 4/20 (20%) | 8 | 1/18 (5.6%) | 2 | 3/18 (16.7%) | 6 | 4/18 (22.2%) | 4 | 8/20 (40%) | 20 |
| Constipation | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 3/20 (15%) | 3 |
| Dental caries | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Diarrhoea | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 3/18 (16.7%) | 4 | 1/18 (5.6%) | 2 | 6/20 (30%) | 8 |
| Faecal incontinence | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Gastrooesophageal reflux disease | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Glossodynia | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Nausea | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 2/18 (11.1%) | 3 | 3/20 (15%) | 5 |
| Retching | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 2 |
| Salivary gland enlargement | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Toothache | 1/20 (5%) | 1 | 2/18 (11.1%) | 2 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 4/20 (20%) | 5 |
| Vomiting | 2/20 (10%) | 3 | 7/18 (38.9%) | 7 | 4/18 (22.2%) | 6 | 12/18 (66.7%) | 26 | 13/20 (65%) | 42 |
| General disorders | ||||||||||
| Application site vesicles | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Catheter site erythema | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 2 |
| Catheter site pain | 3/20 (15%) | 3 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 3/20 (15%) | 4 |
| Chills | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Extravasation | 1/20 (5%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 2 |
| Feeling hot | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Gait disturbance | 2/20 (10%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 |
| Implant site erythema | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 4 | 1/20 (5%) | 4 |
| Implant site extravasation | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Implant site rash | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Influenza like illness | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Infusion site erythema | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 1/20 (5%) | 2 |
| Infusion site inflammation | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Infusion site oedema | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Injection site pain | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 2 |
| Injection site reaction | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Malaise | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 2 | 1/20 (5%) | 3 |
| Pyrexia | 6/20 (30%) | 6 | 9/18 (50%) | 12 | 5/18 (27.8%) | 8 | 10/18 (55.6%) | 20 | 14/20 (70%) | 46 |
| Hepatobiliary disorders | ||||||||||
| Hepatomegaly | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 3 |
| Immune system disorders | ||||||||||
| Drug hypersensitivity | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Hypersensitivity | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Infections and infestations | ||||||||||
| Abdominal abscess | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Catheter site infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Ear infection | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 3/18 (16.7%) | 4 | 5/20 (25%) | 6 |
| Eye infection | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Gastroenteritis viral | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Helminthic infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Impetigo | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 3 | 1/20 (5%) | 3 |
| Infection | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Lice infestation | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 1/20 (5%) | 2 |
| Localised infection | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Lower respiratory tract infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Nail infection | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Nasopharyngitis | 2/20 (10%) | 3 | 3/18 (16.7%) | 3 | 1/18 (5.6%) | 1 | 4/18 (22.2%) | 6 | 8/20 (40%) | 13 |
| Otitis externa | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Pharyngitis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Rhinitis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Skin infection | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Subcutaneous abscess | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Tinea pedis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Tonsillitis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Varicella | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Arthropod bite | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Arthropod sting | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Contusion | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 2/18 (11.1%) | 2 | 2/20 (10%) | 4 |
| Device migration | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 3 |
| Excoriation | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Eye injury | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Face injury | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 2 | 1/20 (5%) | 2 |
| Fall | 2/20 (10%) | 3 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 1/18 (5.6%) | 2 | 5/20 (25%) | 7 |
| Head injury | 2/20 (10%) | 3 | 1/18 (5.6%) | 2 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 4/20 (20%) | 7 |
| Injury | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Joint injury | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Medical device complication | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Mouth injury | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Procedural pain | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Procedural vomiting | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Thermal burn | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Aspartate aminotransferase increased | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Blood immunoglobulin E increased | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Blood immunoglobulin G decreased | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Blood lactate dehydrogenase increased | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Blood sodium increased | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Cardiac murmur | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Computerised tomogram | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Echocardiogram abnormal | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Electrocardiogram T wave amplitude decreased | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Eosinophil count increased | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Nuclear magnetic resonance imaging | 1/20 (5%) | 1 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 4/18 (22.2%) | 4 | 6/20 (30%) | 7 |
| Oxygen saturation decreased | 0/20 (0%) | 0 | 1/18 (5.6%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 3 |
| Protein total abnormal | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Respiratory rate increased | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Weight increased | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Hypercholesterolaemia | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 3/20 (15%) | 3 | 3/18 (16.7%) | 4 | 0/18 (0%) | 0 | 4/18 (22.2%) | 4 | 8/20 (40%) | 11 |
| Back pain | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 3/18 (16.7%) | 4 | 4/20 (20%) | 5 |
| Bursitis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Mobility decreased | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 3/20 (15%) | 3 |
| Muscular weakness | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Neck pain | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Pain in extremity | 4/20 (20%) | 6 | 3/18 (16.7%) | 3 | 1/18 (5.6%) | 1 | 4/18 (22.2%) | 5 | 10/20 (50%) | 15 |
| Pain in jaw | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Nervous system disorders | ||||||||||
| Ageusia | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Clonus | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Dizziness | 2/20 (10%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/20 (10%) | 3 |
| Headache | 4/20 (20%) | 8 | 2/18 (11.1%) | 3 | 1/18 (5.6%) | 8 | 6/18 (33.3%) | 16 | 9/20 (45%) | 35 |
| Lethargy | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Spinal cord compression | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Psychiatric disorders | ||||||||||
| Insomnia | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Renal and urinary disorders | ||||||||||
| Enuresis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Incontinence | 0/20 (0%) | 0 | 1/18 (5.6%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 3 |
| Urinary incontinence | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Reproductive system and breast disorders | ||||||||||
| Balanitis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Penile pain | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/20 (5%) | 1 | 5/18 (27.8%) | 7 | 3/18 (16.7%) | 3 | 10/18 (55.6%) | 18 | 13/20 (65%) | 29 |
| Dry throat | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Dyspnoea | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Epistaxis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Nasal congestion | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 2 | 1/18 (5.6%) | 1 | 3/20 (15%) | 4 |
| Oropharyngeal pain | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 4/18 (22.2%) | 4 | 6/20 (30%) | 6 |
| Pharyngeal oedema | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Productive cough | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Rales | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Wheezing | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermatitis diaper | 1/20 (5%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Dry skin | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 2 |
| Erythema | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 2/20 (10%) | 2 |
| Petechiae | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Pruritus | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Psoriasis | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Rash | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 3/18 (16.7%) | 4 | 4/20 (20%) | 6 |
| Rash generalised | 0/20 (0%) | 0 | 1/18 (5.6%) | 2 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/20 (10%) | 3 |
| Rash maculo-papular | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 3 | 1/20 (5%) | 3 |
| Rash papular | 0/20 (0%) | 0 | 1/18 (5.6%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 3 |
| Rash pruritic | 1/20 (5%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/18 (5.6%) | 2 | 3/20 (15%) | 4 |
| Skin disorder | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 2 | 1/20 (5%) | 2 |
| Skin lesion | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Skin ulcer | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Surgical and medical procedures | ||||||||||
| Cautery to nose | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/20 (5%) | 1 |
| Induction of anaesthesia | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Vascular disorders | ||||||||||
| Flushing | 0/20 (0%) | 0 | 2/18 (11.1%) | 2 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 3/20 (15%) | 4 |
| Hot flush | 0/20 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Hypotension | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
| Poor venous access | 0/20 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/20 (5%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI cannot publish any data prior to multi-centre publication. If publication related to sub-sets of data shall make reference to the relevant multi-centre publication. PI agrees to submit data to Sponsor for review and comment 60 days prior to publication. During review period, Sponsor may request that publication be delayed for up to 6 months from date of first submission to Sponsor in order for Sponsor to take steps to protect its proprietary information.
Results Point of Contact
| Name/Title | BioMarin Medical Information Services |
|---|---|
| Organization | BioMarin Pharmaceutical Inc. |
| Phone | 800-983-4587 |
| medinfo@bmrn.com |
Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00884949
Other Study ID Numbers:
- MOR-002
First Posted:
Apr 21, 2009
Last Update Posted:
Jun 30, 2014
Last Verified:
May 1, 2014